It is proposed that a mutant genotype for a heritable cancer syndrome whose clinical expression is solely in such tissues as the pancreas will be demonstrated by distinctive phenotypes of cells cultured from more readily accessible tissues (i.e., epidermis, dermis, GI mucosa, etc.) even though they do not express the mutation in vivo. For the heritable cancer syndromes involving the pancreas (Familial cancer of the pancreas, familial malignant melanoma, hereditary pancreatitis, multiple familial endocrine adenocarcinomas, Von-Hippel-Lindau, ataxia telangiectasia) the primary objectives are: (1) identify the mutant genotype/s prior to any clinical neoplasms, (2) for use in detection, prevention including genetic counseling. The plan to meet these objectives is to study by clinical and in vitro methodologies the families with such heritable cancer syndromes. Detailed family pedigrees will be developed; the clinical phenotype of the proband and other affected members will be confirmed; cell culture studies will be done on cultures established from tissues with and without the clinical expression to identify the culture phenotype which consistently and reliably reflects the germinal mutation; and clinical, cytogenetic as well as cell culture data will be evaluated through consecutive generations in each family. All data will be correlated to determine the existence of: (1) genetic homogeneity and heterogeneity within family groups which appear on clinical criteria to have the same cancer syndrome with and without cancer genotype expression in the pancreas and (2) new (previously unrecognized) genetic cancer syndromes involving the pancreas. This will be used in improved medical surveillance and family counseling.